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Scientists Prime The Immune System As A Powerful Cancer Weapon

Early results showing that genetically modified white blood cells, called T-cells, can make cancer cells disappear, at least temporarily, in 50% to 90% of patients with certain blood cancers that have failed all other treatments have ignited a land grab among drug companies. But until now it’s been uncertain whether the immune system could be weaponized against solid tumors like those in breast, lung, and cervical cancer. Some doubted that the cells could make it into these cancers, which literally build walls of flesh and blood to protect themselves.

A Human T Cell (Photo credit: NIAID)

Now, in a study presented by scientists from the National Cancer Institute here at the annual meeting of the American Society of Clinical Oncology (ASCO), that question has been answered: at least in principal, the cells can work in a solid tumor, too.

The research was done in nine women with cervical cancer. That disease is a perfect target, because it is caused by a virus – the human papilloma virus, or HPV – that the body already trains white blood cells to recognize. The NCI researchers looked in the blood of eight women for HPV-hunting white cells. They found them in six, grew the cells up, and re-injected them. In three women, tumors shrank substantially. In two of those women, cancers that had spread to other parts of the body disappeared completely, a stunning result, although it is too early to say if the women are cured.

“This proof-of-principal study shows that adoptive transfer of HPV-targeted T cells can cause complete remission of metastatic cervical cancer and that this remission can be long-lasting,” said lead study author Christian Hinrichs in a prepared statement. “One implication of the study is that cellular therapy might have application to a broader range of tumor types than previously recognized. This treatment is still considered experimental and is associated with significant side effects. We also need to explore why this therapy worked so well in certain women, and not in others.”

Other researchers working on cancer cell therapies rejoiced at the result. “It’s great news for the field because it does show that if you can properly isolate T-cells you can make the cancer go away even if it’s metastatic,” says Renier Brentjens, director of the Cellular Therapeutics Center at Memorial Sloan Kettering Cancer Center in New York. “This report gives hope may be a way to treat where standard chemotherapies have failed and maybe replace chemotherapies some day.” He cautions, though, that the cells presented here are just a proof-of-concept. “It’s a model A Ford when you want to build a Ferrari,” he says.

But the result is sure to bolster the already white-hot interest among drug companies and investors in commercializing T-cell therapies. Brentjens is a co-founder of perhaps the hottest company in biotech, a startup called Juno Therapeutics that has raised $175 million from investors including Jeff Bezos. NovartisNovartis has plowed into the field with a licensing deal with the University of Pennsylvania, and says has made genetically modified T-cells a top priority, and is involved in patent litigation with Juno that could help shape the field. Los Angeles-based Kite Pharma has licensed cell therapy tech from the NCI. Cellectis, CelgeneCelgene, and Bluebird Bio are all involved in the field.

This morning, GlaxoSmithKlineGlaxoSmithKline entered the field – countering the perception that its recent sale of its marketed cancer drugs to Novartis would end its research interest – by agreeing to pay biotech AdaptImmune as much as $350 million over seven years to develop another type of T-cell treatment, which it hopes could be better at recognizing a broader swath of cancer cells, says Axel Hoos, who heads immuno-oncology research at GSK.

The cell therapy results come on top of data that will reinforce excitement about another, simpler approach: drugs that block the proteins that cancer cells use as cloaking devices to tell the body’s own T-cells not to attack. These include Yervoy, an approved medication from Bristol-Myers Squibb, and a new generation of drugs called PD-1 inhibitors (PD for the programmed death receptor, a switch on T-cells that tells them to kill the cell they just encountered) that are being developed by Bristol, Merck, Roche, and AstraZeneca and are probably the most-watched drugs in cancer.

This year brings a string of new results for the PD-1 drugs and for Bristol’s trial combining its PD-1 with Yervoy. The results are likely to disappoint some investors because it is still impossible to say if one drug has an edge over another, except that Bristol seems ahead in clinical trials and Merck has filed with the Food and Drug Administration in melanoma patients who have failed Yervoy.

“They all look very similar,” says Jedd Wolchok, a Memorial Sloan Kettering doctor who has been involved in the development of the PD-1 drugs. “It’s still good to hear,” he says, “because it reinforces the idea that immunotherapy is not a treatment for just one or two diseases, it can be applied in numerous diseases.”

On Saturday, researchers presented data on Roche’s drug in bladder cancer. In patients whose tumors expressed PD-L1, the receptor that trips the PD-1 switch on T-cells, 44% of patients saw their tumors shrink. In those without PD-L1, the 10% saw their tumors shrink. In bladder cancer that has failed other treatments, that’s still a good number. Merck released data yesterday showing that its PD-1, pembrolizumab, showed that 20% of patients with head-and-neck cancer responded to its drug, with one patient’s tumors becoming undetectable.

This morning at a press conference researchers are presenting new data for Bristol’s Yervoy, Merck’s pembrolizumab, and the combination of Bristol’s nivolumab and Yervoy in melanoma. Yervoy was effective when used after surgery. But Wolchok cautions that doctors will still need to figure who should get the drug, because some post-surgery patients may have been cured already and Yervoy has toxic side effects like intestinal perforation and liver damage.

In a study of Merck’s pembrolizumab, 69% of 411 patients with metastatic melanoma were still alive at the end of a year. Thirty-four percent of patients saw their tumors shrink substantially, what doctors call a response, and 88% of those tumors were still shrunken at one year.

The combination of nivolumab and Yervoy produced an unprecedented survival rate in a melanoma, with a median survival of 40 months – that’s more than three years. Just a few years ago, median survival was only a year. Twenty-two of the 53 patients (41%) responded to the treatment, and nine (17%) had complete remissions. But 53% of patients had severe side effects, including blood test results that indicate damage to the liver and pancreas.

Those results could be bad for other players in melanoma, because it could mean doctors will usually combine the other drugs with Yervoy and puts Bristol first in line for earlier tests of its drug. In lung cancer, though, a bigger market, results for the combination have been less definitive.

None of these treatments will be cheap. A course of treatment for Yervoy has a list price of $120,000 per patient, although some insurers may negotiate discounts. Nobody expects either the PD-1 inhibitors or cell therapies to be cheap. But they do represent real progress in our long, slow battle against a deadly illness that’s literally written into our genetic code.

“It’s not unreasonable or Pollyanish to think we’re making significant progress in some cancers,” says Brentjens. It could be a first step toward much better treatments for all cancer patients.

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